AbstractID: 8173 Title: Impact of Respiratory Gating Using 4DCT on Therapeutic
Gain (TG) in Patients with Thoracic Malignancies
IMPACT OF RESPIRATORY GATING USING 4DCT ON THERAPEUTIC GAIN (TG) IN
PATIENTS WITH THORACIC MALIGNANCIES
Introduction: Respiration can significantly affect thoracic tumor motion and, therefore the accuracy of
tumor targeting with radiation. 4DCT respiratory gating allows us to quantify the excursion of tumor in
three-dimensions over the course of the respiratory cycle and, therefore to customize tumor margins in
individual patients. This may optimize target coverage and minimize normal tissue exposure to high
radiation dose. This study was undertaken to evaluate the uncomplicated tumor control probability (UTCP)
calculated from the Dosimetry of 4DCT gated treatment plans as compared to traditional non-gated
treatment plans.
Materials and Methods: Lung tumors consist of malignant cells of various degrees of differentiation and,
therefore, different degrees of radiation response. Tumor Control Probability (TCP) provides a quantitative
biophysical measure of tumor dose and has been estimated using the numerically calculated equivalent
uniform dose (EUD) obtained from the dose distributions in the target volume. The concept of EUD
assumes that two different target dose distributions are equivalent if they cause the same radiobiological
effect such that the corresponding number of expected surviving clonogens is equal. TCP mathematically
models tumor response using the / ratio, the clonogen cell density (CCD) and the SF2. Using the linear
quadratic expression for cell killing, we calculated TCP using the following formula:
TCP = e − N ( SF2 )
D α / β +D/ n
Dref α / β + Dref
,
(1)
where N is the number of clonogenic cells in the tumor, calculated by multiplying CCD with tumor
volume; / = 10 Gy, where and are radiosensitivity parameters related to cell killing from single or
multiple hit events respectively. D equals EUD, n equals the number of treatment fractions and SF2 is the
surviving fraction after irradiation at a reference dose (Dref) of 2Gy. Since the population of clonogenic
cells differs in their radioresistance, we assumed a probability distribution of cells surviving at 2 Gray
ranging from 0.1 to 0.5 to generate a weighted SF2. Since CCD may vary from patient to patient and may
also differ within the tumor volume of the same patient, we based our calculation of TCP on CCD of
10M/cc and 220M/cc.
Normal tissues receive radiation dose during the treatment of tumors, and the NTCP is the probability that a
certain percentage of the patient population will incur unfavorable reactions in the contiguous tissue at a
particular dose. We calculated the NTCP of an organ for a uniform dose D to a volume V using LymanKutcher-Burman method, and is given by
1
NTCP =
2π
Where,
t=
t
e −t
2
2
⋅ dt
−∞
(2)
D − TD50 (V )
m ⋅ TD50 (V )
The TD50 (V) is the tolerance dose for a 50% complication probability due to uniform irradiation to a partial
volume V, and is related to the tolerance dose for whole organ TD50 (1), by TD50 (V) = TD50 (1) / (V)n. In
the above equations, parameters m and n deal with slope of the dose response curve and the volume effect
respectively. These parameters and TD50 (1) were obtained from published data.
The therapeutic gain (TG) is obtained by calculating the uncomplicated tumor control probability (UTCP)
which is the probability of tumor control while having no complications using the following formula:
UTCP = (TCP x
i(1-NTCPi)),
(3)
AbstractID: 8173 Title: Impact of Respiratory Gating Using 4DCT on Therapeutic
Gain (TG) in Patients with Thoracic Malignancies
Where, i =1 to 4, represents normal tissues of heart, spinal cord, uninvolved lung and esophagus. Higher
value of UTCP indicates biologically a treatment plan with higher therapeutic gain.
Ten patients underwent treatment planning with gated and non-gated CT. Gated CT images were obtained
at full inspiration, full expiration and at 25th, 50th and 75th percentile of respiration. For non-gated plans, the
planning target volume (PTV) included an all around 1 cm margin for tumor motion and 0.5 cm for set-up
error. For “gated plans”, tumor volumes of individual CT images were superimposed with a 0.5 cm margin
for set-up error. The prescription dose was 60-70 Gy at 2 Gy per fraction. Dose Volume Histograms
(DVH’s) were generated for the PTV’s, heart, spinal cord, esophagus, and total lung in each treatment plan.
For each patient, rival treatment plans achieved with gated and non-gated CT planning were compared on
the basis of TCP, NTCP and TG.
Results: The average gated PTV was 292.7 cc versus 575.2 cc for non gated PTV. TCP was higher for
gated plans. Specifically, TCP was 95.42% and 90.38% for gated plans with CCD of 10M and 220 M,
respectively. For non-gated plans and CCD of 10 M and 220M, TCP was 93.52% and 85.36%, respectively
as shown in Table 1. The gain in terms of normal tissue sparing in the gated treatment plans was also
confirmed by NTCP calculations. Specifically, NTCPs for lung, esophagus, heart and spinal cord were
7.96%, 5.23%, 1.66% and 0.38% with gating versus 26%, 8.25%, 9.36% and 0.52% without gating as
shown in Table 2. The greatest absolute difference in NTCP of 18.04% was observed for lung. The
differences in UTCPs between gated and non gated plans were 26.21% and 24.98% for CCDs of 10M and
220 M, respectively which indicates that the gated plans are clearly superior compared to non gated plans.
Conclusions: 4DCT respiratory gating allows for radiation field reduction, also decreasing doses to lung
and other normal tissues. 4DCT in combination with image guided radiation therapy will improve radiation
target dosing while maximizing normal tissue sparing and may limit the incidence of radiation induced late
toxicity in long –term survivors.
Table 1. Values of TCP for gated and non gated plans
Clonogen Cell Density
Gating (%)
Non-gating (%)
CCD
SF2 weighted
SF2weighted
10 Million
95.42
93.52
220 Million
90.38
85.36
Table 2. Values of NTCP for gated and non gated plans
Organ
Gated (%)
Non-gated (%)
Lung
7.96
26.00
Esophagus
5.23
8.25
Heart
1.66
9.36
Spinal cord
0.38
0.52